Seal Rock Therapeutics unveils NASH-targeting ASK1 inhibitor

Seattle
Seal Rock’s lead asset, dubbed SRT-015, is a liver-selective inhibitor of apoptosis signal-regulating kinase 1, which has shown “promising efficacy” in preclinical models. (Pixabay)

Two years after its founding, Seal Rock Therapeutics is officially launching, with plans to bring its lead asset, an apoptosis signal-regulating kinase 1 (ASK1) inhibitor it is developing for nonalcoholic steatohepatitis (NASH), into human trials in 2020. 

The Seattle-based biotech is a virtual company with a powerful target, said CEO Neil McDonnell. But it’s joining a crowded field that has recently seen a proliferation of new companies—NASH-focused Akero Therapeutics and 89Bio both launched in the past few months—as well as a number of Big Pharmas that are looking to strike gold. 

To McDonnell, the more, the merrier. 

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“NASH is a huge potential disease burden and so, we need drugs right now and we’re going to need more than one mechanism,” he said in an interview. “Different people respond to different things and we all think about combination potential—combinations are going to be where NASH [treatment] goes.” 

Seal Rock’s lead asset, dubbed SRT-015, is a liver-selective inhibitor of ASK1, which has shown “promising efficacy” in preclinical models, the company said in a statement. In a mouse model of NASH, the drug had “statistically significant positive effects on both metabolic parameters and liver-specific pathology.” It also reduced liver fibrosis, abnormal enlargement of the liver, inflammation and steatosis—the abnormal retention of fats in a cell—all of which are key drivers of NASH, Seal Rock said. 

“SRT-015 has a unique property that makes it particularly suitable for NASH: it is distributed to the liver where it is needed, but very little is present in the circulation or other tissues, which helps reduce risk of side effects and may allow for higher, more effective doses,” McDonnell said in the statement. 

“It has a bit of a metabolic effect, but its job is not just to work on that. It inhibits things that are downstream from those metabolic effects,” he said. 

The company is working on IND-enabling studies with plans to file the IND by the first quarter of 2020. A phase 1 study would follow. 

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Seal Rock’s launch comes shortly after that of 89Bio, which is developing an FGF21 analog acquired from Teva for NASH. FGF21, or glycopegylated fibroblast growth factor 21, is a protein that plays a key role in regulating metabolism and signaling throughout the body. However, its half-life is only half an hour, making it unsuitable for treating NASH. Using an analog, such as 89Bio’s BIO89-100, extends the half-life and activity of the native protein. 

Akero is working on its own FGF21 analog, this one licensed from Amgen. AKR-001 has been studied through phase 1 in people with diabetes, and Akero plans to study it through phase 2 in NASH patients. It has a half-life of three to four days, which makes it suitable for once-weekly dosing, according to Akero’s Chief Scientific Officer Tim Rolph.